Woman Underwent Liver Transplantation Research Articles

Induction of CYP3A activity by dexamethasone may not be strong, even at high doses: insights from a case of tacrolimus co-administration

BackgroundDexamethasone (DEX) induces CYP3A activity in a concentration-dependent manner. However, no study has examined changes in the blood concentration of CYP3A substrate drugs when DEX is administered at high doses. Herein, we present a case in which tacrolimus (TAC), a typical CYP3A substrate drug, was co-administered with a chemotherapy regimen that included high-dose DEX.Case presentationA 71-year-old woman underwent liver transplantation for hepatocellular carcinoma 18 years prior to her inclusion in this case study. She was receiving TAC orally at 2 mg/day and had a stable trough blood concentration of approximately 4 ng/mL and a trough blood concentration/dose (C/D) ratio of approximately 2. The patient was diagnosed with post-transplant lymphoproliferative disease (histological type: Burkitt's lymphoma) after admission. Thereafter, the patient received cyclophosphamide-prednisolone (CP), followed by two courses of R-HyperCVAD (rituximab, cyclophosphamide, doxorubicin, vincristine, and DEX) and R-MA (rituximab, methotrexate, and cytarabine) replacement therapy. DEX (33 mg/day) was administered intravenously on days 1–4 and days 11–14 of R-HyperCVAD treatment, and aprepitant (APR) was administered on days 1–5 in both courses. The TAC C/D ratio decreased to approximately 1 on day 11 during both courses, and then increased. Furthermore, a decreasing trend in the TAC C/D ratio was observed after R-MA therapy. The decrease in the TAC C/D ratio was attributed to APR administration rather than to DEX.ConclusionThe induction of CYP3A activity by a high dose of DEX may not be strong. The pharmacokinetic information on DEX and in vitro enzyme activity induction studies also suggested that CYP3A activity induction is not prominent under high-dose DEX treatment.

Acquired partial lipoatrophy as graft-versus-host disease and treatment with metreleptin: two case reports

IntroductionAcquired partial lipoatrophy has been reported after bone marrow transplantation during childhood; however, no adult cases have previously been reported. We herein report two adult cases of acquired partial lipoatrophy after transplantation.Case presentationA 28-year-old Japanese woman developed diabetic ketoacidosis and received insulin therapy after bone marrow transplantation. She manifested partial lipoatrophy of the extremities, prominent insulin resistance, hyperglycemia, hypertriglyceridemia, and fatty liver. A 40-year-old Japanese woman underwent liver transplantation from a living donor for alcoholic liver disease after abstinence from alcohol. She newly developed non-alcoholic steatohepatitis and diabetes. Non-alcoholic steatohepatitis progressed to liver failure, and a second liver transplantation from a brain-dead donor was performed at 42 years of age. She demonstrated loss of subdermal fat of the upper and lower extremities, prominent insulin resistance, hyperglycemia, and hypertriglyceridemia. In both cases, the injection of recombinant methionyl human leptin reversed all of the metabolic abnormalities.ConclusionsAcquired partial lipoatrophy after transplantation is a manifestation of chronic graft-versus-host disease in adults. This entity is associated with diabetes with prominent insulin resistance and severe hypertriglycemia and can be successfully treated with metreleptin for the long term.

Prevalence of Abnormal Pap Smear in Women Undergoing Liver Transplantation [15E

INTRODUCTION: Female patients being evaluated for liver transplantation (LT) routinely undergo a gynecologic exam including cervical cancer screening. The prevalence of cervical cytologic abnormalities in this high risk population is unknown. Our study determines prevalence of cervical cytologic abnormalities, HPV positive status, and risk factors for abnormal cervical screening for this population. METHODS: With Institutional review board approval, we reviewed 375 charts of women undergoing evaluation for LT from 2008‒2013 at Mayo Clinic Florida. We recorded demographics, Pap smear results, High risk HPV positive results, and co-morbid conditions. Univariate analysis was done to determine risk factors. We compared the result of the LT group to the general female population getting cervical cancer screening during the same time period. RESULTS: 37 of 375 (9.86%) LT patients had abnormal Pap smear, compared to 1784 of 26118 (6.83%) of the general population patients (p < 0.01). Among LT patients with cervical cytologic abnormalities, 40.5% were ASCUS, HPV positive (64.8% for non-LT patients), 29.7% were LSIL (28.1% for non-LT patients), 5.4% were HSIL (6.7% for non-LT patients) and 24.3% were cytology negative with HPV positive (0.2% for non-LT patients, p < 0.05). Younger age and presence of hypertension were associated with higher risk of having an abnormal cervical cytology or positive HPV status among LT patients. CONCLUSION: Patients undergoing evaluation for LT have increased prevalence of abnormal cervical cytology, or a positive High risk HPV test. Gynecologic surveillance for this high risk population is recommended.

Features of Patients With Severe Hepatitis Due to Mushroom Poisoning and Factors Associated With Outcome.

Acute liver failure after ingestion of toxic mushrooms is a significant medical problem. Most exposures to toxic mushrooms produce no symptoms or only mild gastroenteritis, but some lead to severe hepatic necrosis and fulminant hepatic failure requiring liver transplantation. We aimed to assess mortality from mushroom poisoning and identify variables associated with survival and liver transplantation. We collected information from 27 patients (13 male; median age, 47 years) admitted to the emergency department within 24 hours of ingesting wild mushrooms. They developed severe liver injury (serum levels of transaminases greater than 400 IU/L) and were treated with activated charcoal and N-acetylcysteine at a tertiary medical center in San Francisco, California from January 1997 through December 2014. Viral hepatitis, autoimmune liver disease, acetaminophen, salicylate toxicity, and chronic liver diseases were ruled out for all patients. We analyzed patient demographics, time since ingestion, presenting symptoms, laboratory values, and therapies administered. A good outcome was defined as survival without need for liver transplant. A poor outcome was defined as death or liver transplant. Positive predictive values were calculated, and the χ2 test was used to analyze dichotomous variables. Liver injury was attributed to ingestion of Amanita phalloides in 24 patients and Amanita ocreata in 3 patients. Twenty-four of the patients ingested mushrooms with meals and 3 patients for hallucinogenic purpose. At 24-48 hours after ingestion, all patients had serum levels of alanine aminotransferase ranging from 554 to 4546 IU/L (median, 2185 IU/L). Acute renal impairment developed in 5 patients. Twenty-three patients survived without liver transplantation, and 4 patients had poor outcomes (1 woman underwent liver transplantation on day 20 after mushroom ingestion, and 3 women died of hepatic failure). Of the 23 patients with peak levels of total bilirubin of 2 mg/dL or more during hospitalization, only 4 had a poor outcome. Peak serum level of aspartate aminotransferase less than 4000 IU/L, peak international normalized ratio less than 2, and a value of serum factor V greater than 30% identified patients with good outcomes with 100% positive predictive value; if these peak values were used as a cutoff, 10 of 27 patients (37%), 7 of 27 patients (26%), and 6 of 12 patients (50%), respectively, could have avoided transfer to a transplant center. In an analysis of 27 patients with hepatocellular damage due to mushroom (Amanita) poisoning and peak levels of total bilirubin greater than 2 mg/dL, the probability of liver transplantation or death is 17%, fulfilling Hy's law. Patients with peak levels of aspartate aminotransferase less than 4000 IU/L can be monitored in a local hospital, whereas patients with higher levels should be transferred to liver transplant centers. Women and older patients were more likely to have a poor outcome than men and younger patients.

Is liver transplantation associated with decreased bone mass in climacteric women?

To evaluate whether climacteric women undergoing liver transplantation had higher prevalence of decreased bone mass than those without any liver disease. A cross-sectional study with 48 women receiving follow-up care at a university hospital in Southeastern Brazil, from February 4th 2009 to January 5th 2011, was conducted. Of these women, 24 were 35 years or older and had undergone liver transplantation at least one year before study entry. The remaining 24 women had no liver disease and their ages and menstrual patterns were similar to those of transplanted patients. Laboratorial tests (follicle-stimulating hormone and estradiol) and bone density measurements of the lumbar spine and femur (equipment Hologic, Discovery WI) were performed. Statistical analysis was carried out by Fisher's exact test, simple Odds Ratio (OR), and multiple logistic regression. Mean age of the women included in the study was 52.8 (± 10.7) years-old, 27.1% were premenopausal and 72.9% were peri/postmenopausal. Approximately 14.6% of these women exhibited osteoporosis and 35.4% had low bone mass. The following items were associated with decreased bone mass: being postmenopausal (OR=71.4; 95%CI 3.8 - 1,339.7; p<0.0001), current age over 49 years-old (OR=11.4; 95%CI 2.9 - 44.0; p=0.0002), and serum estradiol levels lower than 44.5 pg/mL (OR=18.3; 95%CI 3.4 - 97.0; p<0.0001). Having a history of liver transplantation was not associated with decreased bone mass (OR=1.4; 95%CI 0.4 - 4.3; p=0.56). Liver transplantation was not associated with decreased bone mass in this group of climacteric women.

Asymptomatic transmission of Treponema pallidum (syphilis) through deceased donor liver transplantation

A 55-year-old woman underwent liver transplantation (LT) with a graft from a deceased donor. Mandatory pre-donation investigations showed positive syphilis serology that was available only after the transplant, with high Treponema pallidum particle agglutination assay titer compatible with donor syphilis infection. Despite the institution of appropriate post-exposure prophylaxis, the recipient demonstrated latent seroconversion; however, liver graft function improved without evidence of syphilitic hepatitis or other manifestations of the disease. Through this first reported case of asymptomatic transmission of syphilis following LT, we highlight the investigations and treatment strategies for donor-derived syphilis in liver transplant recipients. This report supplements the existing limited evidence on safe use of infected grafts from syphilitic donors through appropriate post-exposure prophylaxis.

Hepatic flow optimization in full right split liver transplantation

Split liver transplantation for two adults offers a valuable opportunity to expand the donor pool for adult recipients. However, its application is mainly hampered by the physiological limits of these partial grafts. Small for size syndrome is a major concern during transplantation with partial graft and different techniques have been developed in living donor liver transplantation to prevent the graft dysfunction. Herein, we report the first application of synergic approaches to optimise the hepatic hemodynamic in a split liver graft for two adults. A Caucasian woman underwent liver transplantation for alcoholic cirrhosis (MELD 21) with a full right liver graft (S5-S8) without middle hepatic vein. Minor and accessory inferior hepatic veins were preserved by splitting the vena cava; V5 and V8 were anastomosed with a donor venous iliac patch. After implantation, a 16G catheter was advanced in the main portal trunk. Inflow modulation was achieved by splenic artery ligation. Intraportal infusion of PGE1 was started intraoperatively and discontinued after 5 d. Graft function was immediate with normalization of liver test after 7 d. Nineteen months after transplantation, liver function is normal and graft volume is 110% of the recipient standard liver volume. Optimisation of the venous outflow, inflow modulation and intraportal infusion of PGE1 may represent a valuable synergic strategy to prevent the graft dysfunction and it may increase the safety of split liver graft for two adults.

Sirolimus addition to tacrolimus-based immunosuppression induces complete remission of post-transplant lymphoproliferative disorder in a liver transplant recipient

Sirolimus addition to tacrolimus-based immunosuppression induces complete remission of post-transplant lymphoproliferative disorder in a liver transplant recipient

Endovascular treatment of supra‐celiac aortic pseudoaneurysms following liver transplantation

The development of supra-celiac pseudoaneurysms following aorto-hepatic reconstruction during liver transplantation represents a major and surgically challenging complication. However, the use of endovascular stent grafts for the exclusion of aortic aneurysms is now a standard procedure with low morbidity and mortality. We demonstrate the successful endovascular repair of three cases of supra-celiac pseudoaneurysms, which developed after liver transplantation. A 40-yr-old woman, a 61-yr-old man, and a 45-yr-old woman underwent liver transplantation for end-stage liver disease. Between three months and five yr after the transplantation the patients developed large supra-celiac pseudoaneurysms leading to thrombosis of the hepatic artery and biliary complications. The stent graft implantation was uneventful, one endoleak Type I occluded spontaneously. There were no intervention-related complications. Unfortunately, one patient died one month after the procedure due to progressive liver failure and one died after five months due to multiple organ failure. One patient is still alive and in good condition.

Liver transplantation for acute liver failure from drug induced liver injury in the United States.

Studies of acute liver failure from drugs have included cases mostly attributed to acetaminophen (APAP) but have reported limited data on other drugs. We used the United Network for Organ Sharing (UNOS) liver transplant database from 1990 to 2002 to identify recipients and estimate a U.S. population-based rate of liver transplantation due to acute liver failure from drugs. Patients were identified if their diagnosis was acute hepatic necrosis from an implicated drug at the time of transplant. Liver transplantation for drug hepatotoxicity accounted for 15% of liver transplants for acute liver failure over the study period. In our cohort (n = 270), 206 (76%) recipients were female. APAP alone, or in combination with another drug, accounted for 133 (49%) cases. In the non-acetaminophen (non-APAP) group (n = 137), the most frequently implicated drugs were: isoniazid, n = 24 (17.5%); propylthiouracil, n = 13 (9.5%); and phenytoin and valproate in 10 (7.3%) cases each. One-year patient and graft survival for the entire cohort was 77 and 71%, respectively. Among Caucasians (n = 206) and African-Americans (n = 48), APAP only was implicated in 110 (53%) patients and 12 (25%) patients, respectively, and non-APAP drugs were implicated in 96 (47%) patients and 36 (75%) patients, respectively (P =.0004). Among African-Americans in the non-APAP group, 28 (78%) were women. In conclusion four drugs were implicated in 42% of patients undergoing liver transplantation for acute liver failure due to drugs other than APAP. The increased frequency of African-American women undergoing liver transplantation for non-APAP drug induced liver injury warrants further study.

Acute vaginal bleeding in women undergoing liver transplantation

OBJECTIVES: Our aim was to define the nature of acute vaginal bleeding problems in women undergoing liver transplantation and to determine the efficacy of treatments given. STUDY DESIGN: We performed a retrospective chart review of 24 patients undergoing liver transplantation in whom consultation was requested for vaginal bleeding. RESULTS: Twenty-four liver transplant patients were seen for evaluation of acute vaginal bleeding. Two patients were seen before transplantation, and 16 women were evaluated for bleeding after transplantation (8 within the first 15 postoperative days). In the other eight women abnormal uterine bleeding developed between 2 months and 5 years after transplantation. Five of these women had compromised liver function. In six other women vaginal bleeding originated from extrauterine sources. Six of seven endometrial biopsy specimens revealed proliferative endometrium, and the other showed adenomatous hyperplasia. Three of four patients had a response to progestational agents, bleeding stopped spontaneously in three patients, two required hysterectomy, and three died of other causes. The other five patients were not seen again by us before or after discharge from the hospital. CONCLUSIONS: Medical or surgical therapy can effectively control acute vaginal bleeding in liver transplant patients. (AM J OBSTET GYNECOL 1994;170:733-6.)

Surgical risk in alcoholic cirrhotic postmenopausal women: Prognostic value of levels of hormones

Because increased prolactin levels and hyperprolactinemia in the presence of encephalopathy in males with cirrhosis (alcohol-induced cirrhosis in particular) are associated with statistically increased mortality, we have examined pre-surgical levels of prolactin and other hormones, as well as the presence of encephalopathy, in 12 postmenopausal women with end-stage alcohol-induced cirrhosis in relation to liver transplant survival. Levels of estradiol were significantly lower, while luteinizing hormone (LH) and 17-hydroxyprogesterone as well as the ratio of estradiol to testosterone were significantly higher prior to transplantation among the women who survived, compared with non-survivors. A similar pattern was seen for transplant candidates who died before transplantation as compared with still-living candidates. These findings suggest that pre-operative levels of sex steroids and pituitary hormones may have prognostic value in alcoholic cirrhotic postmenopausal women undergoing liver transplantation.

Liver transplantation restores female reproductive endocrine function

The effect of successful liver transplantation on menstrual function was assessed by questionnaire in 44 women transplanted for various types of end stage liver disease, acute liver failure or malignant disease. Significant amenorrhoea (>one year) was present in 48% of women with chronic liver disease before transplantation, and was reversed within 10 months of surgery in all but one of the pre-menopausal patients who had primary amenorrhoea and hypogonadotrophic hypogonadism. Two patients became pregnant five months and 1–5 years after transplantation, but in one instance the pregnancy was unsuccessful, possibly as a consequence of cyclosporin related intrauterine growth retardation. Seventeen female patients who underwent orthotopic liver transplantation between June 1973 and June 1987 became pregnant 5 months to 11 years after transplantation. Immunosuppression was maintained with combinations of prednisone, cyclosporine, and azathioprine prior to and during pregnancy. One patient discontinued immunosuppression after knowledge of pregnancy, taking only azathioprine sporadically. Mean age at time of delivery was 26 years. Twelve patients had no alteration in liver function studies; 7 patients demonstrated mild or moderate enzyme elevations prior to delivery, with one case of rejection confirmed by percutaneous liver biopsy. Major problems related to pregnancy were hypertension, anemia, and hyperbilirubinemia. Twenty live births occurred (2 patients had 2 separate pregnancies, one patient has a set of twins); 13 were by caesarian section, 7 by vaginal delivery. Eleven of the 13 caesarian births were premature by gestational age. All vaginal births were term. Toxemia of pregnancy and early rupture of membranes were the principal indications for caesarean section. There were no congenital abnormalities or birth defects and all the children are surviving well. Fifteen of 16 children older than one year have normal physical and mental development, with one child manifesting immature speech development. Four children are under one year, all with normal milestones thus far. Sixteen of the 17 mothers are alive from 2–18 years after transplantation; the only death was from a lymphoma, almost 4 years after transplantation and 2 1/2 years after delivery. This experience suggests that women undergoing liver transplantation can safely bear children despite an increased risk of premature caesarian births. The effect of chronic immunosuppression of female pediatric patients on their reproductive potential later in adulthood remains to be fully evaluated but the results so far are favorable.

CHILDBEARING AFTER LIVER TRANSPLANTATION

Seventeen female patients who underwent orthotopic liver transplantation between June 1973 and June 1987 became pregnant 5 months to 11 years after transplantation. Immunosuppression was maintained with combinations of prednisone, cyclosporine, and azathioprine prior to and during pregnancy. One patient discontinued immunosuppression after knowledge of pregnancy, taking only azathioprine sporadically. Mean age at time of delivery was 26 years. Twelve patients had no alteration in liver function studies; 7 patients demonstrated mild or moderate enzyme elevations prior to delivery, with one case of rejection confirmed by percutaneous liver biopsy. Major problems related to pregnancy were hypertension, anemia, and hyperbilirubinemia. Twenty live births occurred (2 patients had 2 separate pregnancies, one patient had a set of twins); 13 were by cesarean section, 7 by vaginal delivery. Eleven of the 13 cesarean births were premature by gestational age. All vaginal births were term. Toxemia of pregnancy and early rupture of membranes were the principal indications for cesarean section. There were no congenital abnormalities or birth defects and all the children are surviving well. Fifteen of 16 children older than one year all have normal physical and mental development, with one child manifesting immature speech development. Four children are under one year, all with normal milestones thus far. Sixteen of the 17 mothers are alive from 2-18 years after transplantation; the only death was from a lymphoma, almost 4 years after transplantation and 2 1/2 years after delivery. This experience suggests that women undergoing liver transplantation can safely bear children despite an increased risk of premature cesarean births. The effect of chronic immunosuppression of female pediatric patients on their reproductive potential later in adulthood remains to be fully evaluated but the results so far are favorable.